Celastrol suppresses nitric oxide synthases and the angiogenesis pathway in colorectal cancer

Gao, Yanfeng; Zhou, Shuang; Pang, Lizhi; Yang, Jianfeng; Li, Han John; Huo, Xiongwei; Qian, Steven Y.

doi:10.1080/10715762.2019.1575512

Cited by 39 publications

(27 citation statements)

References 44 publications

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“…Our recent study [ 66 ] demonstrated that celastrol (tripterine), extracted from the thunder god vine, inhibited the activities of iNOS and eNOS in CRC cells. The inhibitory effects in cell growth and migration were associated with the angiogenesis pathway.…”

Section: Nos Inhibitors: Targeting Nos In Colon Cancermentioning

confidence: 99%

Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer

Wang

Xie

et al. 2020

Cancers

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Colorectal cancer (CRC) is one of the most lethal malignancies worldwide and CRC therapy remains unsatisfactory. In recent decades, nitric oxide (NO)—a free-radical gas—plus its endogenous producer NO synthases (NOS), have attracted considerable attention. NO exerts dual effects (pro- and anti-tumor) in cancers. Endogenous levels of NO promote colon neoplasms, whereas exogenously sustained doses lead to cytotoxic functions. Importantly, NO has been implicated as an essential mediator in many signaling pathways in CRC, such as the Wnt/β-catenin and extracellular-signal-regulated kinase (ERK) pathways, which are closely associated with cancer initiation, metastasis, inflammation, and chemo-/radio-resistance. Therefore, NO/NOS have been proposed as promising targets in the regulation of CRC carcinogenesis. Clinically relevant NO-donating agents have been developed for CRC therapy to deliver a high level of NO to tumor sites. Notably, inducible NOS (iNOS) is ubiquitously over-expressed in inflammatory-associated colon cancer. The development of iNOS inhibitors contributes to targeted therapies for CRC with clinical benefits. In this review, we summarize the multifaceted mechanisms of NO-mediated networks in several hallmarks of CRC. We review the clinical manifestation and limitations of NO donors and NOS inhibitors in clinical trials. We also discuss the possible directions of NO/NOS therapies in the immediate future.

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Section: Nos Inhibitors: Targeting Nos In Colon Cancermentioning

confidence: 99%

Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer

Wang

Xie

et al. 2020

Cancers

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“…Suppression of the expression of key genes (TYMP, CDH5, THBS2, LEP, MMP9, and TNF) and proteins (IL-1b, MMP-9, PDGF, Serpin E1, and TIMP-4) involved in the angiogenesis pathway [495]. Reduces the cell size of the SP (side population) increases frequency of apoptosis and binds to Pgp protein in cell membranes inhibiting its transport function [496]. Inhibits CRC cell proliferation and migration through suppression of MMP3 and MMP7 by the PI3K/AKT signaling pathway [497].…”

Section: Rootmentioning

confidence: 99%

Alternative Treatments for Cancer Prevention and Cure [Part 1]

Mohiuddin¹

2019

APCT

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Many lay people along with some so called "key opinion leaders" have a common slogan "There's no answer for cancer". Again, mistake delays proper treatment and make situation worse, more often. Compliance is crucial to obtain optimal health outcomes, such as cure or improvement in QoL. Patients may delay treatment or fail to seek care because of high out-of-pocket expenditures. Despite phenomenal development, conventional therapy falls short in cancer management. There are two major hurdles in anticancer drug development: dose-limiting toxic side effects that reduce either drug effectiveness or the QoL of patients and complicated drug development processes that are costly and time consuming. Cancer patients are increasingly seeking out alternative medicine and might be reluctant to disclose its use to their oncology treatment physicians. But there is limited available information on patterns of utilization and efficacy of alternative medicine for patients with cancer. As adjuvant therapy, many traditional medicines shown efficacy against brain, head and neck, skin, breast, liver, pancreas, kidney, bladder, prostate, colon and blood cancers. The literature reviews non-pharmacological interventions used against cancer, published trials, systematic reviews and meta-analyses.

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“…It is a potent antioxidant evidenced by inhibiting lipid peroxidation (Bian et al 2016) and an antiinflammatory agent by balancing pathogenic and regulatory T cells (Astry et al 2015). What's more, it exhibits an anti-cancer capacity evidenced by anti-angiogenic properties (Gao et al 2019). However, there are few reports that tripterine has shown clinical activity in scarring formation.…”

Section: Introductionmentioning

confidence: 99%

Tripterine emerges as a potential anti-scarring agent in NIH/3T3 cells by repressing ANRIL

Jiang¹,

Sun²,

Wang³

2020

gpb

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Extensive scarring normally causes hypertrophic or keloid scars. This intuitively results in psychosocial distress and reduction in life quality. Tripterine is a bioactive pentacyclic triterpenoid compound while it is still poorly understood whether it possesses an anti-scarring function. NIH/3T3 cells were administrated with tripterine at increased concentrations (0-10 μM). Antisense RNA to INK4 locus (ANRIL) was transformed into NIH/3T3 cells, and the cells transfected with empty vector (mock transfection) were used as negative control. Then, cell viability and migration were profiled by cell counting kit-8 (CCK-8) and 24-Transwell assay. Protein expression was analyzed by Western blot assay. ANRIL was quantified by quantitative reverse transcription-PCR (qRT-PCR). Tripterine administration induced the growth inhibition of NIH/3T3 cells indicated by a trend toward the decreased expression of matrix metallopeptidase (MMPs), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). This process was accompanied by the decreased phosphorylation of p65, inhibitor of nuclear factor kappa-B alpha (IκBα) and the downregulation of β-catenin. Moreover, ANRIL expression was notably repressed by tripterine. By contrast, in ANRIL-transfected cells, the effect of tripterine was abolished. Tripterine exhibited an anti-scarring bioactivity in NIH/3T3 cells by inhibiting ANRIL, and this process was accompanied by the blockade of nuclear factor-kappa B (NF-κB) and β-catenin cascades.

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Celastrol suppresses nitric oxide synthases and the angiogenesis pathway in colorectal cancer

Cited by 39 publications

References 44 publications

Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer

Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer

Alternative Treatments for Cancer Prevention and Cure [Part 1]

Tripterine emerges as a potential anti-scarring agent in NIH/3T3 cells by repressing ANRIL

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